APPLICANT'S ABSTRACT: Asians, as a whole, have lower rates of alcohol abuse and alcohol dependence than most other ethnic groups. This decreased risk for alcoholism is thought to result from a combination of biological and sociocultural factors. In the biological realm, recent research has focused on the role of genetically determined factors, such as polymorphisms of the alcohol metabolizing enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), as responsible for alcohol-induced flushing, differences in alcohol and acetaldehyde degradation, and some of the observed ethnic differences in the incidence of alcoholism. There is little information, however, about how these enzyme polymorphisms actually influence an individual's drinking behavior or how sociocultural variables might interact with these biological variables. Pilot data suggest that some Asians may experience a qualitatively, and perhaps quantitatively, different reaction to alcohol. Additional research is needed to evaluate the impact of specific polymorphisms of the alcohol metabolizing enzymes and their interaction with sociocultural variables on individual response to alcohol. This project will use a between-group, repeated measures design to test response to both placebo and alcohol administration among men and women of Asian heritage with different ADH2, ADH3, and ALDH2 genotypes. This study will focus on various measures of reaction to alcohol and alcohol metabolism. Measures of reaction to alcohol will include subjective feelings of intoxication, heart rate, blood pressure, facial flushing, facial blood flow, plasma cortisol and ACTH levels, and EEG measures. Alcohol metabolism will be measured by blood alcohol concentrations (BACS) and acetaldehyde levels. Sociocultural variables (e.g., specific Asian ethnicity, number of generations lived in the United States, and level of acculturation into American society), factors that may indirectly affect response to alcohol, either through differential levels of experience with alcohol or through learned responses (e.g., cultural attitudes toward drinking or expectations of alcohol's effects) will also be assessed. It is hypothesized that individuals with ALDH2*2 alleles will demonstrate enhanced responses to alcohol compared with subjects with only ALDH2*1 alleles. It is also hypothesized that, independent of ALDH2*2 alleles, subjects with ADH2*2, and ADH3*1 alleles will have more intense responses to alcohol than subjects with ADH2*1 and ADH3*2 alleles. This study will also analyze data as a way to examine whether the response to alcohol of Asian women differs from that of Asian men, to determine if sociocultural factors explain some of the variability in alcohol sensitivity, and to explore possible mediating and moderating variables associated with intensity of alcohol intoxication and alcohol consumption patters. The proposed research is part of an effort to elucidate genetically determined responses to alcohol and has the potential to provide critical information for understanding how ADH and ALDH genes might interact with other important variables to modify alcohol drinking and protection from alcoholism among Asian men and women.